Public Health Impact of Paxlovid as Treatment for COVID-19, United States.

We evaluated the population-level benefits of expanding treatment with the antiviral drug Paxlovid (nirmatrelvir/ritonavir) in the United States for SARS-CoV-2 Omicron variant infections. Using a multiscale mathematical model, we found that treating 20% of symptomatic case-patients with Paxlovid over a period of 300 days beginning in January 2022 resulted in life and cost savings. In a low-transmission scenario (effective reproduction number of 1.2), this approach could avert 0.28 million (95% CI 0.03-0.59 million) hospitalizations and save US $56.95 billion (95% CI US $2.62-$122.63 billion). In a higher transmission scenario (effective reproduction number of 3), the benefits increase, potentially preventing 0.85 million (95% CI 0.36-1.38 million) hospitalizations and saving US $170.17 billion (95% CI US $60.49-$286.14 billion). Our findings suggest that timely and widespread use of Paxlovid could be an effective and economical approach to mitigate the effects of COVID-19.

Freedom of choice adds value to public goods.

Public goods, ranging from judiciary to sanitation to parkland, permeate daily life. They have been a subject of intense interdisciplinary study, with a traditional focus being on participation levels in isolated public goods games (PGGs) as opposed to a more recent focus on participation in PGGs embedded into complex social networks. We merged the two perspectives by arranging voluntary participants into one of three network configurations, upon which volunteers played a number of iterated PGGs within their network neighborhood. The purpose was to test whether the topology of social networks or a freedom to express preferences for some local public goods over others affect participation. The results show that changes in social networks are of little consequence, yet volunteers significantly increase participation when they freely express preferences. Surprisingly, the increase in participation happens from the very beginning of the game experiment, before any information about how others play can be gathered. Such information does get used later in the game as volunteers seek to correlate contributions with higher returns, thus adding significant value to public goods overall. These results are ascribable to a small number of behavioral phenotypes, and suggest that societies may be better off with bottom-up schemes for public goods provision.

Autopoietic Influence Hierarchies in Pancreatic ß Cells.

ß cells are biologically essential for humans and other vertebrates. Because their functionality arises from cell-cell interactions, they are also a model system for collective organization among cells. There are currently two contradictory pictures of this organization: the hub-cell idea pointing at leaders who coordinate the others, and the electrophysiological theory describing all cells as equal. We use new data and computational modeling to reconcile these pictures. We find via a network representation of interacting ß cells that leaders emerge naturally (confirming the hub-cell idea), yet all cells can take the hub role following a perturbation (in line with electrophysiology).

Beyond ranking nodes: Predicting epidemic outbreak sizes by network centralities.

Identifying important nodes for disease spreading is a central topic in network epidemiology. We investigate how well the position of a node, characterized by standard network measures, can predict its epidemiological importance in any graph of a given number of nodes. This is in contrast to other studies that deal with the easier prediction problem of ranking nodes by their epidemic importance in given graphs. As a benchmark for epidemic importance, we calculate the exact expected outbreak size given a node as the source. We study exhaustively all graphs of a given size, so do not restrict ourselves to certain generative models for graphs, nor to graph data sets. Due to the large number of possible nonisomorphic graphs of a fixed size, we are limited to ten-node graphs. We find that combinations of two or more centralities are predictive (R2 scores of 0.91 or higher) even for the most difficult parameter values of the epidemic simulation. Typically, these successful combinations include one normalized spectral centrality (such as PageRank or Katz centrality) and one measure that is sensitive to the number of edges in the graph.

ß Cells Operate Collectively to Help Maintain Glucose Homeostasis.

Residing in the islets of Langerhans in the pancreas, ß cells contribute to glucose homeostasis by managing the body's insulin supply. Although it has been acknowledged that healthy ß cells engage in heavy cell-to-cell communication to perform their homeostatic function, the exact role and effects of such communication remain partly understood. We offer a novel, to our knowledge, perspective on the subject in the form of 1) a dynamical network model that faithfully mimics fast calcium oscillations in response to above-threshold glucose stimulation and 2) empirical data analysis that reveals a qualitative shift in the cross-correlation structure of measured signals below and above the threshold glucose concentration. Combined together, these results point to a glucose-induced transition in ß-cell activity thanks to increasing coordination through gap-junctional signaling and paracrine interactions. Our data and the model further suggest how the conservation of entire cell-cell conductance, observed in coupled but not uncoupled ß cells, emerges as a collective phenomenon. An overall implication is that improving the ability to monitor ß-cell signaling should offer means to better understand the pathogenesis of diabetes mellitus.

Efficient sentinel surveillance strategies for preventing epidemics on networks.

Surveillance plays a crucial role in preventing emerging infectious diseases from becoming epidemic. In circumstances where it is possible to monitor the infection status of certain people, transport hubs, or hospitals, early detection of the disease allows interventions to be implemented before most of the damage can occur, or at least its impact can be mitigated. This paper addresses the question of which nodes we should select in a network of individuals susceptible to some infectious disease in order to minimize the number of casualties. By simulating disease outbreaks on a collection of empirical and synthetic networks we show that the best strategy depends on topological characteristics of the network. For highly modular or spatially embedded networks it is better to place the sentinels on nodes distributed across different regions. However, if the degree heterogeneity is high, then a strategy that targets network hubs is preferred. We further consider the consequences of having an incomplete sample of the network and demonstrate that the value of new information diminishes as more data is collected. Finally we find further marginal improvements using two heuristics informed by known results in graph theory that exploit the fragmented structure of sparse network data.

Advantage of Being Multicomponent and Spatial: Multipartite Viruses Colonize Structured Populations with Lower Thresholds.

Multipartite viruses have a genome divided into different disconnected viral particles. A majority of multipartite viruses infect plants; very few target animals. To understand why, we use a simple, network-based susceptible-latent-infectious-recovered model. We show both analytically and numerically that, provided that the average degree of the contact network exceeds a critical value, even in the absence of an explicit microscopic advantage, multipartite viruses have a lower threshold to colonizing network-structured populations compared to a well-mixed population. We further corroborate this finding on two-dimensional lattice networks, which better represent the typical contact structures of plants.

Heterogeneous cooperative leadership structure emerging from random regular graphs.

This paper investigates the evolution of cooperation and the emergence of hierarchical leadership structure in random regular graphs. It is found that there exist different learning patterns between cooperators and defectors, and cooperators are able to attract more followers and hence more likely to become leaders. Hence, the heterogeneous distributions of reputation and leadership can emerge from homogeneous random graphs. The important directed game-learning skeleton is then studied, revealing some important structural properties, such as the heavy-tailed degree distribution and the positive in-in degree correlation.

Cost-efficient vaccination protocols for network epidemiology.

We investigate methods to vaccinate contact networks-i.e. removing nodes in such a way that disease spreading is hindered as much as possible-with respect to their cost-efficiency. Any real implementation of such protocols would come with costs related both to the vaccination itself, and gathering of information about the network. Disregarding this, we argue, would lead to erroneous evaluation of vaccination protocols. We use the susceptible-infected-recovered model-the generic model for diseases making patients immune upon recovery-as our disease-spreading scenario, and analyze outbreaks on both empirical and model networks. For different relative costs, different protocols dominate. For high vaccination costs and low costs of gathering information, the so-called acquaintance vaccination is the most cost efficient. For other parameter values, protocols designed for query-efficient identification of the network's largest degrees are most efficient.

Solving the Dynamic Correlation Problem of the Susceptible-Infected-Susceptible Model on Networks.

The susceptible-infected-susceptible (SIS) model is a canonical model for emerging disease outbreaks. Such outbreaks are naturally modeled as taking place on networks. A theoretical challenge in network epidemiology is the dynamic correlations coming from that if one node is infected, then its neighbors are likely to be infected. By combining two theoretical approaches-the heterogeneous mean-field theory and the effective degree method-we are able to include these correlations in an analytical solution of the SIS model. We derive accurate expressions for the average prevalence (fraction of infected) and epidemic threshold. We also discuss how to generalize the approach to a larger class of stochastic population models.

Predictability of population displacement after the 2010 Haiti earthquake.

Most severe disasters cause large population movements. These movements make it difficult for relief organizations to efficiently reach people in need. Understanding and predicting the locations of affected people during disasters is key to effective humanitarian relief operations and to long-term societal reconstruction. We collaborated with the largest mobile phone operator in Haiti (Digicel) and analyzed the movements of 1.9 million mobile phone users during the period from 42 d before, to 341 d after the devastating Haiti earthquake of January 12, 2010. Nineteen days after the earthquake, population movements had caused the population of the capital Port-au-Prince to decrease by an estimated 23%. Both the travel distances and size of people's movement trajectories grew after the earthquake. These findings, in combination with the disorder that was present after the disaster, suggest that people's movements would have become less predictable. Instead, the predictability of people's trajectories remained high and even increased slightly during the three-month period after the earthquake. Moreover, the destinations of people who left the capital during the first three weeks after the earthquake was highly correlated with their mobility patterns during normal times, and specifically with the locations in which people had significant social bonds. For the people who left Port-au-Prince, the duration of their stay outside the city, as well as the time for their return, all followed a skewed, fat-tailed distribution. The findings suggest that population movements during disasters may be significantly more predictable than previously thought.

Epidemiologically optimal static networks from temporal network data.

One of network epidemiology's central assumptions is that the contact structure over which infectious diseases propagate can be represented as a static network. However, contacts are highly dynamic, changing at many time scales. In this paper, we investigate conceptually simple methods to construct static graphs for network epidemiology from temporal contact data. We evaluate these methods on empirical and synthetic model data. For almost all our cases, the network representation that captures most relevant information is a so-called exponential-threshold network. In these, each contact contributes with a weight decreasing exponentially with time, and there is an edge between a pair of vertices if the weight between them exceeds a threshold. Networks of aggregated contacts over an optimally chosen time window perform almost as good as the exponential-threshold networks. On the other hand, networks of accumulated contacts over the entire sampling time, and networks of concurrent partnerships, perform worse. We discuss these observations in the context of the temporal and topological structure of the data sets.

Nonrepresentativeness of Human Mobility Data and its Impact on Modeling Dynamics of the COVID-19 Pandemic: Systematic Evaluation.

BACKGROUND: In recent years, a range of novel smartphone-derived data streams about human mobility have become available on a near-real-time basis. These data have been used, for example, to perform traffic forecasting and epidemic modeling. During the COVID-19 pandemic in particular, human travel behavior has been considered a key component of epidemiological modeling to provide more reliable estimates about the volumes of the pandemic's importation and transmission routes, or to identify hot spots. However, nearly universally in the literature, the representativeness of these data, how they relate to the underlying real-world human mobility, has been overlooked. This disconnect between data and reality is especially relevant in the case of socially disadvantaged minorities. OBJECTIVE: The objective of this study is to illustrate the nonrepresentativeness of data on human mobility and the impact of this nonrepresentativeness on modeling dynamics of the epidemic. This study systematically evaluates how real-world travel flows differ from census-based estimations, especially in the case of socially disadvantaged minorities, such as older adults and women, and further measures biases introduced by this difference in epidemiological studies. METHODS: To understand the demographic composition of population movements, a nationwide mobility data set from 318 million mobile phone users in China from January 1 to February 29, 2020, was curated. Specifically, we quantified the disparity in the population composition between actual migrations and resident composition according to census data, and shows how this nonrepresentativeness impacts epidemiological modeling by constructing an age-structured SEIR (Susceptible-Exposed-Infected- Recovered) model of COVID-19 transmission. RESULTS: We found a significant difference in the demographic composition between those who travel and the overall population. In the population flows, 59% (n=20,067,526) of travelers are young and 36% (n=12,210,565) of them are middle-aged (P<.001), which is completely different from the overall adult population composition of China (where 36% of individuals are young and 40% of them are middle-aged). This difference would introduce a striking bias in epidemiological studies: the estimation of maximum daily infections differs nearly 3 times, and the peak time has a large gap of 46 days. CONCLUSIONS: The difference between actual migrations and resident composition strongly impacts outcomes of epidemiological forecasts, which typically assume that flows represent underlying demographics. Our findings imply that it is necessary to measure and quantify the inherent biases related to nonrepresentativeness for accurate epidemiological surveillance and forecasting.

Information dynamics shape the sexual networks of Internet-mediated prostitution.

Like many other social phenomena, prostitution is increasingly coordinated over the Internet. The online behavior affects the offline activity; the reverse is also true. We investigated the reported sexual contacts between 6,624 anonymous escorts and 10,106 sex buyers extracted from an online community from its beginning and six years on. These sexual encounters were also graded and categorized (in terms of the type of sexual activities performed) by the buyers. From the temporal, bipartite network of posts, we found a full feedback loop in which high grades on previous posts affect the future commercial success of the sex worker, and vice versa. We also found a peculiar growth pattern in which the turnover of community members and sex workers causes a sublinear preferential attachment. There is, moreover, a strong geographic influence on network structure--the network is geographically clustered but still close to connected, the contacts consistent with the inverse-square law observed in trading patterns. We also found that the number of sellers scales sublinearly with city size, so this type of prostitution does not, comparatively speaking, benefit much from an increasing concentration of people.

Gender inequality and self-publication are common among academic editors.

Scientific editors shape the content of academic journals and set standards for their fields. Yet, the degree to which the gender makeup of editors reflects that of scientists, and the rate at which editors publish in their own journals, are not entirely understood. Here, we use algorithmic tools to infer the gender of 81,000 editors serving more than 1,000 journals and 15 disciplines over five decades. Only 26% of authors in our dataset are women, and we find even fewer women among editors (14%) and editors-in-chief (8%). Career length explains the gender gap among editors, but not editors-in-chief. Moreover, by analysing the publication records of 20,000 editors, we find that 12% publish at least one-fifth, and 6% publish at least one-third, of their papers in the journal they edit. Editors-in-chief tend to self-publish at a higher rate. Finally, compared with women, men have a higher increase in the rate at which they publish in a journal soon after becoming its editor.

The nature and nurture of network evolution.

Although the origin of the fat-tail characteristic of the degree distribution in complex networks has been extensively researched, the underlying cause of the degree distribution characteristic across the complete range of degrees remains obscure. Here, we propose an evolution model that incorporates only two factors: the node's weight, reflecting its innate attractiveness (nature), and the node's degree, reflecting the external influences (nurture). The proposed model provides a good fit for degree distributions and degree ratio distributions of numerous real-world networks and reproduces their evolution processes. Our results indicate that the nurture factor plays a dominant role in the evolution of social networks. In contrast, the nature factor plays a dominant role in the evolution of non-social networks, suggesting that whether nodes are people determines the dominant factor influencing the evolution of real-world networks.

Protocol for the automatic extraction of epidemiological information via a pre-trained language model.

The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et al.2.

The public health impact of Paxlovid COVID-19 treatment in the United States.

The antiviral drug Paxlovid has been shown to rapidly reduce viral load. Coupled with vaccination, timely administration of safe and effective antivirals could provide a path towards managing COVID-19 without restrictive non-pharmaceutical measures. Here, we estimate the population-level impacts of expanding treatment with Paxlovid in the US using a multi-scale mathematical model of SARS-CoV-2 transmission that incorporates the within-host viral load dynamics of the Omicron variant. We find that, under a low transmission scenario Re∼1.2 treating 20% of symptomatic cases would be life and cost saving, leading to an estimated 0.26 (95% CrI: 0.03, 0.59) million hospitalizations averted, 30.61 (95% CrI: 1.69, 71.15) thousand deaths averted, and US$52.16 (95% CrI: 2.62, 122.63) billion reduction in health- and treatment-related costs. Rapid and broad use of the antiviral Paxlovid could substantially reduce COVID-19 morbidity and mortality, while averting socioeconomic hardship.

Exploring maps with greedy navigators.

During the last decade of network research focusing on structural and dynamical properties of networks, the role of network users has been more or less underestimated from the bird's-eye view of global perspective. In this era of global positioning system equipped smartphones, however, a user's ability to access local geometric information and find efficient pathways on networks plays a crucial role, rather than the globally optimal pathways. We present a simple greedy spatial navigation strategy as a probe to explore spatial networks. These greedy navigators use directional information in every move they take, without being trapped in a dead end based on their memory about previous routes. We suggest that the centralities measures have to be modified to incorporate the navigators' behavior, and present the intriguing effect of navigators' greediness where removing some edges may actually enhance the routing efficiency, which is reminiscent of Braess's paradox. In addition, using samples of road structures in large cities around the world, it is shown that the navigability measure we define reflects unique structural properties, which are not easy to predict from other topological characteristics. In this respect, we believe that our routing scheme significantly moves the routing problem on networks one step closer to reality, incorporating the inevitable incompleteness of navigators' information.

Simulated epidemics in an empirical spatiotemporal network of 50,185 sexual contacts.

Sexual contact patterns, both in their temporal and network structure, can influence the spread of sexually transmitted infections (STI). Most previous literature has focused on effects of network topology; few studies have addressed the role of temporal structure. We simulate disease spread using SI and SIR models on an empirical temporal network of sexual contacts in high-end prostitution. We compare these results with several other approaches, including randomization of the data, classic mean-field approaches, and static network simulations. We observe that epidemic dynamics in this contact structure have well-defined, rather high epidemic thresholds. Temporal effects create a broad distribution of outbreak sizes, even if the per-contact transmission probability is taken to its hypothetical maximum of 100%. In general, we conclude that the temporal correlations of our network accelerate outbreaks, especially in the early phase of the epidemics, while the network topology (apart from the contact-rate distribution) slows them down. We find that the temporal correlations of sexual contacts can significantly change simulated outbreaks in a large empirical sexual network. Thus, temporal structures are needed alongside network topology to fully understand the spread of STIs. On a side note, our simulations further suggest that the specific type of commercial sex we investigate is not a reservoir of major importance for HIV.